Prediction of impending mood episode recurrence using real-time digital phenotypes in major depression and bipolar disorders in South Korea: a prospective nationwide cohort study.

BACKGROUND: Mood disorders require consistent management of symptoms to prevent recurrences of mood episodes. Circadian rhythm (CR) disruption is a key symptom of mood disorders to be proactively managed to prevent mood episode recurrences. This study aims to predict impending mood episodes recurrences using digital phenotypes related to CR obtained from wearable devices and smartphones. METHODS: The study is a multicenter, nationwide, prospective, observational study with major depressive disorder, bipolar disorder I, and bipolar II disorder. A total of 495 patients were recruited from eight hospitals in South Korea. Patients were followed up for an average of 279.7 days (a total sample of 75 506 days) with wearable devices and smartphones and with clinical interviews conducted every 3 months. Algorithms predicting impending mood episodes were developed with machine learning. Algorithm-predicted mood episodes were then compared to those identified through face-to-face clinical interviews incorporating ecological momentary assessments of daily mood and energy. RESULTS: Two hundred seventy mood episodes recurred in 135 subjects during the follow-up period. The prediction accuracies for impending major depressive episodes, manic episodes, and hypomanic episodes for the next 3 days were 90.1, 92.6, and 93.0%, with the area under the curve values of 0.937, 0.957, and 0.963, respectively. CONCLUSIONS: We predicted the onset of mood episode recurrences exclusively using digital phenotypes. Specifically, phenotypes indicating CR misalignment contributed the most to the prediction of episodes recurrences. Our findings suggest that monitoring of CR using digital devices can be useful in preventing and treating mood disorders.

Addendum to the Acknowledgements: Mood Prediction of Patients With Mood Disorders by Machine Learning Using Passive Digital Phenotypes Based on the Circadian Rhythm: Prospective Observational Cohort Study.

[This corrects the article DOI: 10.2196/11029.].

Mood Prediction of Patients With Mood Disorders by Machine Learning Using Passive Digital Phenotypes Based on the Circadian Rhythm: Prospective Observational Cohort Study.

BACKGROUND: Virtually, all organisms on Earth have their own circadian rhythm, and humans are no exception. Circadian rhythms are associated with various human states, especially mood disorders, and disturbance of the circadian rhythm is known to be very closely related. Attempts have also been made to derive clinical implications associated with mood disorders using the vast amounts of digital log that is acquired by digital technologies develop and using computational analysis techniques. OBJECTIVE: This study was conducted to evaluate the mood state or episode, activity, sleep, light exposure, and heart rate during a period of about 2 years by acquiring various digital log data through wearable devices and smartphone apps as well as conventional clinical assessments. We investigated a mood prediction algorithm developed with machine learning using passive data phenotypes based on circadian rhythms. METHODS: We performed a prospective observational cohort study on 55 patients with mood disorders (major depressive disorder [MDD] and bipolar disorder type 1 [BD I] and 2 [BD II]) for 2 years. A smartphone app for self-recording daily mood scores and detecting light exposure (using the installed sensor) were provided. From daily worn activity trackers, digital log data of activity, sleep, and heart rate were collected. Passive digital phenotypes were processed into 130 features based on circadian rhythms, and a mood prediction algorithm was developed by random forest. RESULTS: The mood state prediction accuracies for the next 3 days in all patients, MDD patients, BD I patients, and BD II patients were 65%, 65%, 64%, and 65% with 0.7, 0.69, 0.67, and 0.67 area under the curve (AUC) values, respectively. The accuracies of all patients for no episode (NE), depressive episode (DE), manic episode (ME), and hypomanic episode (HME) were 85.3%, 87%, 94%, and 91.2% with 0.87, 0.87, 0.958, and 0.912 AUC values, respectively. The prediction accuracy in BD II patients was distinctively balanced as high showing 82.6%, 74.4%, and 87.5% of accuracy (with generally good sensitivity and specificity) with 0.919, 0.868, and 0.949 AUC values for NE, DE, and HME, respectively. CONCLUSIONS: On the basis of the theoretical basis of chronobiology, this study proposed a good model for future research by developing a mood prediction algorithm using machine learning by processing and reclassifying digital log data. In addition to academic value, it is expected that this study will be of practical help to improve the prognosis of patients with mood disorders by making it possible to apply actual clinical application owing to the rapid expansion of digital technology.

Correlation of occupational stress with depression, anxiety, and sleep in Korean dentists: cross-sectional study.

BACKGROUND: This study aimed to investigate the degree of occupational stress and the clinical mental state of dentists. In addition, we investigated the correlation of occupational stress with depression, anxiety, and sleep among dentists in Korea. METHODS: A cross-sectional survey on 231 dentists was conducted using the Doctor Job Stress Scale, Center for Epidemiologic Studies Depression Scale (CES-D), State-Trait Anxiety Index (STAI), and Pittsburgh Sleep Quality Index (PSQI). Correlation of occupational stress with mental health was investigated by adjusted multiple regression analysis. RESULTS: The scores of CES-D, STAI, and PSQI revealed a significant correlation with the Doctor Job Stress Scale (t = 3.93, P < 0.0001; t = 4.05, P < 0.0001; t = 4.18, P < 0.0001, respectively). In particular, patient factors and clinical responsibility/judgment factors were significantly associated with depression (t = 2.80, P = 0.0056; t = 4.93, P < 0.0001, respectively), anxiety (t = 2.35, P = 0.0195; t = 5.11, P < 0.0001, respectively), and sleep (t = 3.78, P = 0.0002; t = 4.30, P < 0.0001, respectively), whereas work factors were not associated with any mental health state. CONCLUSIONS: This study confirms that dentists as professions experience more severe mental states. For successful mental health care among dentists, stress management focusing on interpersonal relationship with patients and responsibility as an expert rather than the intensity of work should be considered.

Gaba transporter SLC6A11 gene polymorphism associated with tardive dyskinesia.

BACKGROUND: Gamma-aminobutyric acid (GABA) insufficiency has been reported to be related to the tardive dyskinesia (TD) susceptibility. Inada et al. (Pharmacogenet Genomics 2008;18:317-23) identified eight genes belonging to GABA receptor signaling pathway that may be involved in TD susceptibility by genome-wide screening and they replicated associations in an independent sample for polymorphisms in SLC6A11 (GABA transporter 3), GABRG3 (c-3 subunit of GABA-A receptor) and GABRB2 (ß-2 subunit of GABA-A receptor). In this study, we tried to replicate their finding in a larger Korean sample and find if any of the genes was associated with the susceptibility to TD. METHODS: We selected three polymorphisms in SLC6A11 (rs4684742), GABRG3 (rs2061051) and GABRB2 (rs918528) from the previous study. We carried out a case-control study (105 TD and 175 non-TD schizophrenic patients) to identify the association between the three candidate polymorphisms and susceptibility to TD and their epistatic interactions by using the multifactor dimensionality reduction (MDR) algorithm. RESULTS: Among the three variants, SCL6A11 genotypes distribution showed a significant difference between the TD and non-TD patients (P = 0.049). However, GABRG3 and GABRB2 genotype distributions were not associated with TD (P = 0.268 and P = 0.976, respectively). Further, our analyses provided significant evidence for gene-gene interactions (SCL6A11, GABRG3 and GABRB2) in the development of TD. The odds ratio increased to 2.53 (CI = 1.515-4.217, P = 0.0003) when the genetic susceptibility to TD was analyzed with the three genes considered altogether through MDR approach. CONCLUSION: These results suggest that GABA receptor signaling pathway was associated with the increased susceptibility to TD in Korean schizophrenic patients.

Daily Self-Monitoring and Feedback of Circadian Rhythm Measures in Major Depression and Bipolar Disorder Using Wearable Devices and Smartphones-The Circadian Rhythm for Mood (CRM®) Trial Protocol: A Randomized Sham Controlled Double-Blind Trial.

The circadian rhythm for mood (CRM) is a digital therapeutic, which aims to prevent mood episode and improve clinical course in patients with major mood disorders. Developed on the circadian rhythm hypothesis of mood disorder, CRM predicts the impending risk of mood episode with its built-in algorithm, utilizing wearable devices data and daily self-reports, and provides personalized feedback. In a pilot study of the CRM, the users experienced less frequent and shorter duration of mood episodes than the non-users. To investigate the efficacy of the upgraded CRM, a double-blind, randomized, sham-controlled, parallel-group trial is designed. Patients aged between 19 and 70, diagnosed with bipolar I disorder, bipolar II disorder, or major depressive disorder, in a euthymic state for more than two months, can participate. During this 12-month trial, participants are assessed for episode recurrence every three months, and the efficacy of the CRM as a potential digital therapeutic is evaluated. Trial registration: ClinicalTrials.gov Identifier: NCT05400785.

Apnea-related sleep fragmentation and poor vigilance in children with well-controlled asthma.

It has been reported that sleep problems and neurocognitive deficit in asthmatic children is prevalent. However, systematic studies on these problems in stable asthma using polysomnography have rarely been performed. We therefore investigated sleep and neurocognitive functioning in children with well-controlled asthma. Forty-three children with well-controlled, stable asthma and 31 controls (age range: 6-9 years) were enrolled in the study. Subjects were questioned for daytime sleepiness using the Paediatric Daytime Sleepiness Scale. Complete overnight polysomnography and neurocognitive function tests were performed on all subjects. Children with stable asthma had lower pulmonary function in comparison to their age-matched controls. Asthmatic children had a higher apnea-hypopnea index (P < 0.001) and apnea-hypopnea-related arousal index (P < 0.001) as compared with non-asthmatics. Deep sleep was decreased in asthmatics (P = 0.001). In the vigilance test, the mean number of correct answers was lower (P = 0.005) and the mean reaction time was slower (P = 0.002) in asthmatic children. A hierarchical multiple linear regression showed that deep sleep and apnea-hypopnea-related arousal index were significant predictors of vigilance. The data suggest that the prevalence of paediatric sleep-disordered breathing and sleep fragmentation could be very high among children with well-controlled asthma. Moreover, vigilance, the ability to maintain attention and alertness, was worse in stable asthmatic children when compared with healthy controls. Sleep-disordered breathing should be checked even in stable asthmatic children as they are at risk for developing neurobehavioural deterioration associated with frequent arousals during sleep. Furthermore, early treatment for asthma may be required in order to prevent airway remodelling that could cause sleep problems.

The BTBD9 gene may be associated with antipsychotic-induced restless legs syndrome in schizophrenia.

OBJECTIVE: A genome-wide association study and several replication studies have shown significant association between BTBD9 gene single nucleotide polymorphisms and restless legs syndrome (RLS). The aim of this study is to investigate the association between the BTBD9 gene polymorphisms and antipsychotic-induced RLS in schizophrenic patients. METHODS: Restless legs syndrome symptoms were evaluated using the diagnostic criteria of the International Restless Legs Syndrome Study Group in 190 Korean schizophrenic patients. We genotyped the rs9357271 and rs3923809 polymorphisms of the BTBD9 gene in schizophrenic patients with (n = 96) and without (n = 94) RLS symptoms. RESULTS: There was a significant difference in the allele frequency (χ(2) = 8.14, p = 0.004) of the rs9357271 polymorphism between schizophrenic patients with and without RLS symptoms. Significant genotypic association of this single nucleotide polymorphisms with RLS symptoms was also observed for the dominant model (χ(2) = 10.32, p = 0.001) and heterozygous model (χ(2) = 10.9, p = 0.001). When we compared the frequencies of the rs3923809-rs9357271 haplotypes between the two groups, the overall haplotype frequencies were significantly different (permuted p = 0.037), and the A-T haplotype was significantly more frequent in the RLS symptom group than in the no RLS symptom group (0.112 vs. 0.041, permuted p = 0.007). CONCLUSIONS: These data suggest that the BTBD9 gene is associated with antipsychotic-induced RLS symptoms in schizophrenic patients.

There is no evidence for an association between the serotonin receptor 3A gene C178T polymorphism and tardive dyskinesia in Korean schizophrenia patients.

BACKGROUND: Tardive dyskinesia (TD) is a potential adverse effect of long-term treatment with antipsychotics. Previous studies have suggested a link between brain serotonergic systems and TD vulnerability. A recent report described that a serotonin 3 receptor (5-HTR3) agonist induced rhythmic movements in mice with complete paraplegia. Furthermore, it has been reported that the 5-HTR3 antagonist ondansetron is efficacious in the treatment of Gilles de la Tourette syndrome (GTS). AIM: The aim of the present study was to determine whether the 5-HTR3A gene C178T polymorphism is associated with antipsychotic-induced TD in Korean schizophrenia patients. METHODS: We investigated 280 Korean schizophrenia patients. Subjects with TD (n = 105) and without TD (n = 175) were matched for antipsychotic drug exposure and other relevant variables. RESULTS: The distributions of genotypic (chi-squared = 3.55, p = 0.169) and allelic (chi-squared = 0.40, p = 0.528) frequencies did not differ between patients with and without TD. The total score on the Abnormal Involuntary Movement Scale also did not differ between the two genotype groups (F = 0.94, p = 0.391). CONCLUSIONS: The findings of the present study do not support the involvement of the 5-HTR3A gene C178T polymorphism in TD in Korean schizophrenia subjects.

Role of cytokines in atypical depression.

BACKGROUND: Atypical depression (AD) is considered a biologically and psychologically distinct subtype of depression. AD, contrary to melancholic depression (MD), may have different alteration in cytokine activity. AIMS: We aimed to investigate the differences of cytokine activity between AD patients and MD patients. Among psychiatric patients visited to the Psychiatry Department, Korea University Medical Center, 105 patients with major depression who met the Diagnostic and Statistical Manual (DSM-IV) criteria based on clinical interviews using a Structured Clinical Interview for DSM-IV were recruited. Among 105 patients, 35 patients had atypical feature. We measured in vitro cytokines (interleukins) IL-2, IL-4, IL-6 and tumor necrosis factor-α (TNF-α). RESULTS: Decreased IL-4 and increased IL-2 was observed in AD patients. IL-6 and TNF-α level of AD patients showed no difference from the controls. CONCLUSIONS: Contrary to MD, AD has reversed vegetative symptoms, i.e. hypersomnia and hyperphagia. It is assumed that the phenotype difference between AD and MD might be related to Th1 cytokines (IL-2) and Th2 cytokines (IL-4) and not related to monocytic cytokines (IL-6, and TNF-α).

PER2 variation is associated with diurnal preference in a Korean young population.

The PER2 gene has been reported to influence diurnal preference. In this study, we have attempted to characterize the associations between the PER2 gene polymorphisms and diurnal preference in a population of healthy young subjects, controlling for the social and environmental confounding factors. Subjects were 299 students in a college, carefully selected to be mentally and physically healthy. All subjects completed the 13-item composite scale for morningness (CSM). PER2 gene polymorphisms were genotyped by PCR-based methods. Genotype and allele carrier status of a PER2 G3853A polymorphism (rs934945) were associated with CSM scores. Carriers of the 3853G allele showed significantly higher CSM scores (P = 0.004, P = 0.009, and P = 0.001; total, morningness, and activity plan, respectively). There were no significant differences on CSM scores among genotypes and allele status of PER2 rs2304672. This result indicates that rs934945 of PER2 may be associated with diurnal preference in a Korean healthy population.

Cannabinoid type 1 receptor gene polymorphisms are not associated with olanzapine-induced weight gain.

BACKGROUND: Olanzapine is an atypical antipsychotic known to cause considerable weight gain. The cannabinoid type 1 receptor has been reported to be involved in energy balance control, appetite stimulation, and increases in body weight. METHODS: In the present study, we investigated three polymorphisms (rs1049353, rs806368, and rs4707436) in the cannabinoid type 1 receptor gene (CNR1) and weight gain in Korean patients with schizophrenia receiving olanzapine treatment. Weight and height were measured prior to starting olanzapine and again after long-term treatment in 78 patients with schizophrenia. CNR1 polymorphisms were genotyped using PCR-RFLP methods. RESULTS: The three CNR1 polymorphisms were not associated with body weight changes from baseline to the endpoint after olanzapine treatment (p > 0.05). There were also no significant differences in genotype, allele, or haplotype frequencies between the high weight gain (at least 7%) and low weight gain (less than 7%) groups. CONCLUSION: Within the limitations imposed by the smallness of the clinical sample, our findings suggest that CNR1 polymorphisms are not associated with olanzapine-induced weight gain.

Association study between antipsychotic-induced restless legs syndrome and polymorphisms of monoamine oxidase genes in schizophrenia.

OBJECTIVE: This study aimed to investigate whether the monoamine oxidase (MAO) A and B genes are associated with antipsychotic-induced restless legs syndrome (RLS) in schizophrenia. METHODS: We assessed antipsychotic-induced RLS symptoms in 190 Korean schizophrenic patients and divided the subjects into two groups: those with RLS symptoms (n = 96) and those without RLS symptoms (n = 94). Genotyping was performed for the variable number of tandem repeat (VNTR) polymorphism of the MAOA gene and A644G polymorphism of the MAOB gene. RESULTS: There was no significant difference in the genotype and allele frequencies of all polymorphisms investigated between these two groups. However, the result of global haplotype analysis showed a significant difference in haplotype frequencies between male subjects with and without RLS symptoms (p = 0.013). The interaction between two polymorphisms had a significant effect on the RLS scores of both male (p = 0.047) and female (p = 0.028) patients. CONCLUSIONS: These data do not suggest that the MAOA gene VNTR and MAOB gene A644G polymorphisms are associated with antipsychotic-induced RLS symptoms in schizophrenia. However, we found that the haplotype frequencies differed between the male schizophrenic patients with and without RLS symptom and the interaction between the two polymorphisms had a significant influence on the RLS scores of patients with schizophrenia.

Association between weekend catch-up sleep and high-sensitivity C-reactive protein levels in adults: a population-based study.

STUDY OBJECTIVES: To investigate the association between weekend catch-up sleep (WCS) and the levels of high-sensitivity C-reactive protein (hsCRP)-a serum inflammatory maker-in adults. METHODS: Data of 5,506 adults aged 19 years or older were obtained from the nationwide cross-sectional Korea National Health and Nutrition Examination Surveys conducted in 2016. Serum hsCRP level, weekday and weekend sleep durations, and sociodemographic and health-related characteristics were assessed. Participants whose weekend sleep duration was more than 1 h longer than their weekday sleep duration were included in the WCS group. hsCRP level was categorized into quartiles (i.e. highest, middle-high, middle-low, and lowest). Obesity was defined by body mass index ≥ 25.0 kg/m2. RESULTS: The WCS group included 1,901 participants (34.5%). In the logistic regression analysis controlling for all variables, adults in the WCS group were significantly less likely to show the highest hsCRP level (versus the lowest level) compared with those without WCS in the complete sample (adjusted odds ratio = 0.795, 95% confidence interval [CI] = 0.662 to 0.955). In a subgroup analysis, this association was significant only for those with weekday sleep duration of 6 h or lower. Longer WCS (≥3 h) was not associated with hsCRP levels. Non-obese people with WCS demonstrated a lower risk for high hsCRP levels, while there was no significant difference in obese people with WCS. CONCLUSIONS: Our findings indicate that WCS may be beneficial for low-grade systemic inflammation in adults, particularly among those with shorter weekday sleep durations. WCS may also interact with obesity.

Temporal association between zolpidem medication and the risk of suicide: A 12-year population-based, retrospective cohort study.

There have been concerns about abuse and unnecessary chronic administration of zolpidem, and zolpidem's relation to suicide risk. To investigate the temporal association of zolpidem with the risk of suicide, we conducted a 12-year, population-based, retrospective cohort study on the National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea. Data were collected from 2002 to 2013 from the NHIS-NSC, and data cleaning was performed for 1,125,691 subjects. Cox proportional hazards regression analysis was used to investigate the correlation over time between zolpidem medication and suicide. Over intervals commencing after 80 months of observation, the adjusted hazard ratio of suicides associated with the use of the zolpidem was 2.01 (95% CI: 1.58-2.56; p < 0.001). The mean cumulative number of days of zolpidem prescription was significantly longer in the suicide group than in the non-suicide group after log-transformation (p = 0.005). Cases of chronic use of zolpidem (over six months or one year) were significantly more common in the suicide group compared to the non-suicide group (p = 0.002 and 0.005, respectively). Subjects who received zolpidem medication had a significantly higher risk of suicide after at least 80 months of observation, suggesting a long-term increased suicide risk associated with insomnia exposed to zolpidem medication.

Effectiveness of a Smartphone App With a Wearable Activity Tracker in Preventing the Recurrence of Mood Disorders: Prospective Case-Control Study.

BACKGROUND: Smartphones and wearable devices can be used to obtain diverse daily log data related to circadian rhythms. For patients with mood disorders, giving feedback via a smartphone app with appropriate behavioral correction guides could play an important therapeutic role in the real world. OBJECTIVE: We aimed to evaluate the effectiveness of a smartphone app named Circadian Rhythm for Mood (CRM), which was developed to prevent mood episodes based on a machine learning algorithm that uses passive digital phenotype data of circadian rhythm behaviors obtained with a wearable activity tracker. The feedback intervention for the CRM app consisted of a trend report of mood prediction, H-score feedback with behavioral guidance, and an alert system triggered when trending toward a high-risk state. METHODS: In total, 73 patients with a major mood disorder were recruited and allocated in a nonrandomized fashion into 2 groups: the CRM group (14 patients) and the non-CRM group (59 patients). After the data qualification process, 10 subjects in the CRM group and 33 subjects in the non-CRM group were evaluated over 12 months. Both groups were treated in a similar manner. Patients took their usual medications, wore a wrist-worn activity tracker, and checked their eMoodChart daily. Patients in the CRM group were provided with daily feedback on their mood prediction and health scores based on the algorithm. For the CRM group, warning alerts were given when irregular life patterns were observed. However, these alerts were not given to patients in the non-CRM group. Every 3 months, mood episodes that had occurred in the previous 3 months were assessed based on the completed daily eMoodChart for both groups. The clinical course and prognosis, including mood episodes, were evaluated via face-to-face interviews based on the completed daily eMoodChart. For a 1-year prospective period, the number and duration of mood episodes were compared between the CRM and non-CRM groups using a generalized linear model. RESULTS: The CRM group had 96.7% fewer total depressive episodes (n/year; exp ß=0.033, P=.03), 99.5% shorter depressive episodes (total; exp ß=0.005, P<.001), 96.1% shorter manic or hypomanic episodes (exp ß=0.039, P<.001), 97.4% fewer total mood episodes (exp ß=0.026, P=.008), and 98.9% shorter mood episodes (total; exp ß=0.011, P<.001) than the non-CRM group. Positive changes in health behaviors due to the alerts and in wearable device adherence rates were observed in the CRM group. CONCLUSIONS: The CRM app with a wearable activity tracker was found to be effective in preventing and reducing the recurrence of mood disorders, improving prognosis, and promoting better health behaviors. Patients appeared to develop a regular habit of using the CRM app. TRIAL REGISTRATION: ClinicalTrials.gov NCT03088657; https://clinicaltrials.gov/ct2/show/NCT03088657.

Restless legs syndrome and periodic limb movements during sleep probably associated with olanzapine.

We report five cases of restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) that were probably associated with olanzapine. The first patient showed a good response to olanzapine, but the RLS symptoms associated with olanzapine resulted in poor long-term compliance, eventually leading to frequent relapse of psychotic symptoms. The second patient exhibited sudden PLMS following olanzapine injection. The third patient had been suffering from serious akathisia while on risperidone, and was cured after switching to olanzapine, but thereafter the patient suffered from RLS at nighttime. The fourth patient showed RLS symptoms that were initially caused by a 20-mg daily olanzapine dosage and were later mitigated when olanzapine was reduced and ropinirole was administered. The fifth patient exhibited paraesthesia and agitation caused by olanzapine that was misdiagnosed as psychotic agitation. Increasing the olanzapine dosage severely aggravated the symptoms of RLS. Antipsychotic-induced RLS and PLMS are not well-recognized side effects of antipsychotics, with the symptoms often misdiagnosed as psychotic agitation. These cases also suggest that the occurrence of RLS can cause noncompliance with antipsychotics in psychiatric patients, and thus aggravate their psychotic symptoms.

Association study between glutathione S-transferase GST-M1, GST-T1, and GST-P1 polymorphisms and tardive dyskinesia.

OBJECTIVES: Data from several studies suggest that oxidative stress may play a role in the pathophysiology of tardive dyskinesia (TD). Glutathione S-transferase (GST) enzymes play important roles in protecting cells against oxidative stress. In the present study, we investigated the hypothesis that polymorphisms in genes for these detoxifying enzymes can influence susceptibility to TD in patients with schizophrenia. METHODS: The GST-M1, GST-T1, and GST-P1 loci were analyzed by polymerase chain reaction (PCR)-based methods in 83 schizophrenic patients with TD and 126 schizophrenic without TD who were matched for antipsychotic drug exposure and other relevant variables. The multifactor dimensionality reduction (MDR) approach was used to analyze gene-gene interactions. RESULTS: There were no significant differences in the distributions of the GST-M1, GST-T1, and GST-P1 genotypes between the TD and non-TD groups (p > 0.05). However, in comparison of the severity of TD among genotypes using Poisson regression showed that Ile/Ile genotype of GST-P1 had higher AIMS score compared to Ile/Val + Val/Val genotypes (X(2) = 7.13, p = 0.008). MDR analysis did not show a significant interaction between the three GST gene variants and susceptibility to TD (p > 0.05). CONCLUSIONS: These results suggest that GST gene polymorphisms do not confer increased susceptibility to TD in patients with schizophrenia but TD severity might be related with GST-P1 variants.

No association between the brain-derived neurotrophic factor gene Val66Met polymorphism and tardive dyskinesia in schizophrenic patients.

OBJECTIVE: This study investigated whether the brain-derived neurotrophic factor (BDNF) gene Val66Met single-nucleotide polymorphism (SNP) is associated with antipsychotic-induced tardive dyskinesia (TD) in schizophrenia. METHODS: Genotyping was performed for the BDNF gene Val66Met SNP in Korean schizophrenic patients with (n=83) and without TD (n=126) who were matched for antipsychotic drug exposure and other relevant variables. RESULTS: The frequencies of genotypes (chi2=2.37, p=0.306) and alleles (chi2=0.03, p=0.867) did not differ significantly between these two groups. CONCLUSION: These findings suggest that the BDNF polymorphism does not play a major role in the susceptibility to TD in schizophrenic patients.

Possible association between the -2548A/G polymorphism of the leptin gene and olanzapine-induced weight gain.

Antipsychotic-induced weight gain has important effects on treatment compliance and long-term health. Several reports have indicated that a -2548A/G single-nucleotide polymorphism (SNP) of the leptin gene is associated with antipsychotic-induced weight gain. We hypothesized that there is a similar relationship between the -2548A/G SNP and olanzapine-induced weight gain. A total of 74 Korean schizophrenic patients were examined. Their weight was measured before starting olanzapine and after long-term treatment lasting for at least 3 months. The weight gain was significantly higher for patients with the AG genotype than for those with the AA genotype (p=0.029). Analysis of covariance also showed the difference of weight gain was still significant when adjusted for sex and treatment duration (p=0.046). This finding supports the presence of a relationship between the -2548A/G SNP of the leptin gene and weight gain in Korean schizophrenic patients receiving olanzapine treatment.